Patients with well-documented chronic hepatitis C are being evaluated to determine the long-term natural history of this common form of chronic liver disease. A cohort of such patients are available to evaluate experimental therapies. Previous studies have shown that alpha interferon therapy has a short-term beneficial effect in approximately 50 per cent of patients. This response is sustained in approximately 20 per cent after stopping interferon. A randomized, placebo-controlled trial of ribavirin showed that a 1 year course of this nucleoside analogue is associated with significant improvement in serum aminotransferase activities and in hepatic lobular necrosis despite unchanged serum levels of HCV RNA. Continous ribavirin therapy for up to 2 years demonstrated the practicality of long term supressive therapy in this disease. A trial of escalating doses with alpha interferon is underway. Studies in the first twenty patients reveals that one half of nonresponder patients will respond to higher doses of interferon with loss of HCV RNA from serum. Further follow-up is necessary to show that these responders to higher doses maintain the response when interferon is stopped. A trial has been designed for therapy of patients who do not respond to alpha interferon alone using the combination of interferon and ribavirin.